title: YAP and TAZ regulate skin wound healing.
abstract: The Hippo signaling pathway regulates organ size, tissue regeneration, and stem cell self-renewal. The two key downstream transcription coactivators in this pathway, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), mediate the major gene regulation and biological functions of the Hippo pathway. The biological functions of YAP and TAZ in many tissues are known; however, their roles in skin wound healing remain unclear. To analyze whether YAP and/or TAZ are required for cutaneous wound healing, we performed small interfering RNA (siRNA)-mediated knockdown of YAP/TAZ in full-thickness skin wounds. YAP is strongly expressed in the nucleus and cytoplasm in the epidermis and hair follicle. Interestingly, YAP is expressed in the nucleus in the dermis at 2 and 7 days after wounding. TAZ normally localizes to the cytoplasm in the dermis but is distributed in both the nucleus and cytoplasm at 1 day after wounding. The knockdown of YAP and TAZ markedly delayed the rate of wound closure and reduced the transforming growth factor-β1 (TGF-β1) expression in the wound. YAP and TAZ also modulate the expression of TGF-β1 signaling pathway components such as Smad-2, p21, and Smad-7. These results suggest that YAP and TAZ localization to the nucleus is required for skin wound healing.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: School of Life Science and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Byun
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors.forename: Makoto
authors.initials: M
authors.lastname: Furutani-Seiki
authors.affiliation: School of Life Science and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, Korea; Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR. Electronic address: hsjung@yuhs.ac.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D020405:Dermis / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D004817:Epidermis / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D000090683:Hippo Signaling Pathway; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse; D017346:Protein Serine-Threonine Kinases